The research, involving the growth of cerebral ‘organoids’ from human stem cells, was published in Nature on Wednesday. For some good coverage of the science behind this work, see Ed Yong’s piece here and the FAQ here.

It’s not hard to see why these little blobs have attracted a lot of media attention. It’s a remarkable technique, although growing brain cells in culture is not new. Such ‘brains in a dish’ have been around for some time.

What’s new here is that these organoids grew in 3D, and – all by themselves – started to differentiate into rudimentary brain regions.

Incredible. But is it ethical?

There are, perhaps, three ways to look at this. Firstly, you might feel that such research is repellent by its very nature – that to dissect the human brain in this way is “playing God”, or some such.

Second, you might decide that there are no ethical concerns, because it’s just a bunch of cells. You might consider the notion of worrying about the morality of neural cultures to be silly. Or – what amounts to the same thing – you might never think about the ethics at all.

Now, as a neurobiologist I would love it if there were no ethical dimensions to this. It would make things a lot easier. But I’m not so sure.

We are our brains. You don’t need a liver, a mouth, or legs to be a human being. So if it were possible to somehow grow a complete human brain – complete with the kind of connections found in normal human brains – I think that brain would be a human being.

It would be a human being in a hellish predicament. I think we ought to make sure nothing like that happens. It might seem fanciful, but every human brain started out as a single cell.

We’re several lightyears away from that point right now. The organoids they just made are, for one thing, really small. They reached a maximum diameter of about 4 mm.

This makes them vastly smaller than the brain of a human.

But, then again, 4 mm across isn’t all that much smaller than the brain of a mouse. Mice are not very clever. But I consider it wrong to cause a mouse to suffer unnecessarily – or to put it another way, to cause a mouse brain to suffer. Many people agree.

Find a way to grow these organoids a little bit bigger, and they’d be the size of a mouse brain.

But by itself, this wouldn’t mean much. Human spinal ganglia are in the same ballpark size as 4mm organoids, and mouse brains. Yet we each have dozens of these little bunches of nerve cells, in our backs. They are not known for their intelligence, or capacity to feel pain.

The difference between ganglia and mice is the organization of the neurons. This, rather than size, is what really matters. So I’d say it would only be unethical to create a culture with sufficiently developed connections that it crossed some threshold of complexity.

If you oppose animal experimentation as a whole, you would probably set that threshold pretty low.

But even if you accept doing things to animals, you wouldn’t want to do the same things to humans. There has to be a threshold somewhere.

As to how close we are to reaching it, or how we would possibly know if we’d crossed it, that’s where we bump up against the hardest problems in neuroscience.

My gut feeling is that a neuronal culture wouldn’t develop ‘sufficient connections’ in the absence of any sensory input. But we really don’t know, nor do we know what sufficient connections look like.

So the funny thing is, doing this kind of research is probably the only way we’ll ever work out whether it’s ethical or not.

Interesting thoughts. However, a rain is only a ‘brain’ if it is connected to the outside world. Neurosurgery is painless once you get into the brain, because there are no pain receptors. So one could grow a neurosphere the size of a whale and it still would not be a brain. On the other hand, grow a 0,5 mm neurosphere such as these, with sensory neurons connecting somehow to the outside world and you do have a brain. So perphaps the threshold has to involve connectivity and sensing.

http://brightumbra.wordpress.com/ BrightUmbra

I wonder what it’s like to be a neuron that’s just recently been suddenly excised from its supporting environment; suddenly no longer able to receive information from its neighbors, no longer able to broadcast its distress…

http://brightumbra.wordpress.com/ BrightUmbra

Excellent, excellent article, but please, never use the phrase “lightyears away” unless you’re talking about how far away two things are. A lightyear is a measurement of distance, not time. =)

Meanwhile… while I agree with the main point of your argument, you say: “There has to be a threshold somewhere.” Where would you suggest we place it? What level of complexity is sufficient to permit a sense of awareness, or suffering?

Can other apes suffer the way a human can suffer? Can dolphins, dogs, or cats? Other mammals? What about reptiles or birds? Frogs and turtles? Goldfish? Insects? Worms?

I don’t know.

Sean Rowshandel

We cause ourselves (most importantly) and others to suffer with the back-assward way we manage ourselves here, and our science can’t even grow a brain that would show us how transient our implanted individualitiez are, so that maybe we would change the way we do things– I see a massive human-rights victory at stake here.

Philippa Doran

When does a human brain become aware? Is a 22 week foetus aware? A few have survived. How much earlier could a developing brain become aware?

http://bebrainfit.com/ Deane Alban

Drug companies have been constantly thwarted to find viable treatments for brain diseases such as Alzheimer’s. One major reason is that studies are usually done on rats, but what works in rat brains rarely translates to working in human brains. This groundbreaking discovery at least could be good news for rats which could soon be replaced with lab-grown organs.

Scientists surely will not stop at this pea-sized brain they’ve developed and will continue to push to create bigger, more complex, and more human-like brains. At what point will these tissues be capable of thought, awareness, or consciousness? No one really knows for sure.

David Fuchs

Silly thought. What if we use human brain cells and trigger mouse style epigenomic growth? That way we would be working on human brains at the complexity of a mouse.

This is a great achievement I would say, if it weren’t for the fact that it falls in the middle of an ethical and moral minefield. I do agree that there should be “a threshold somewhere”, because I think that if further research will bring about the development of more complex brains, such brains could perhaps be able to feel or make actual thoughts and then, it would be equivalent to experimenting or testing on a live human, giving rise to even more strong opposition and controversy. However I do agree that actually determining where this “threshold” shoud be would be difficult and perhaps not possible until such brain is actually made in the lab.

I say this is a great achievement because if all the ethical and moral issues could ever be over looked (which I, however, think is not really probable), then these lab grown brains could provide a very efficient way to test for treatments for various brain-related disorders, without actually testing on humans or just limiting to results obtained from mice or other test subjects.

http://www.blogger.com/profile/00171002438761303983 Chrystal Ocean

I don’t consider research unethical by its very nature, and I am generally thrilled by the explorations and discoveries of science. However, I am glad someone is asking this question. It’s one that occurred to me when I read of this research.

http://neuroautomaton.com/ Zachary Stansfield

I’m a little worried that you have gone fast and loose with
your own commentary here, NS. For example, you argue that “We are our brains. You don’t need a liver, a mouth, or legs to be a human being.”

But, this line of reasoning is clearly flawed. I might not need individual parts of my body like a leg or a mouth to be considered human,
but neither would I need individual parts of my brain like the occipital cortex or pineal gland. Indeed, even in cases of severe hydranencephaly we still consider these individuals to be “people”, despite the obvious fact that they lack most normal cognitive functions.

So, while I agree with your general point that “connectivity”
may be used as (one of many) criteria for identifying the level of complexity of a human brain, it is by no means a sufficient criterion. In fact, I would argue that we “do really know” that cultured neural tissue, having developed in the absence of any sensory input or motor output—that is, tissue which entirely lacks a “body”—could not, in any practical sense, develop into the sort of entity that earns the status of “person”.

http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

Hmm.

The point about people lacking certain brain regions is a good one – but one could argue that in such cases, they do have a “human brain”, albeit one somewhat smaller than usual (the parts they do have, are human.)

But fundamentally I stand by what I said. If you waved a magic wand and destroy my entire body, leaving just the brain, I would survive (if the brain could be kept alive in a vat.) That’s not true if you replace “brain” by any other organ.

Now logically then, if my brain (as it stands today, with all the connections) were to be grown in a vat – then that would be me.

If my brain’s in a vat, it doesn’t matter whether it got there by growing, or by removal from a head… surely. That’s just history.

Now it seems that the only question is, if a brain were grown in a vat, could it possibly develop the same connections etc. that a normal brain did?

And that really reduces to the question of blank slate vs. innate wiring. Which is an open question.

http://neuroautomaton.com/ Zachary Stansfield

Even given the “brain in a vat” case, I think this is a much less open question than you let on.

Let’s take the magic wand operation. If I could remove my brain and disconnect it from the outside world (e.g. cut the optic and auditory nerves, sever the spinal cord, etc), but maintain it in a perfusion system that efficiently transports nutrients and waste, then the connections of this brain will shift–likely quite dramatically–and many connections may start to degenerate due to the absence of appropriate sensory input. There might be a period over which this brain is still be able to perform some of the conscious functions that a live, adult person can perform–but this conjecture is unproven. This problem might be alleviated by hooking up the brain to an electronic system that can handle some input and output functions–but this would run contrary to your argument.

On the other hand, if we were to grow a brain in a vat (that is, a culture system) from day one, using techniques similar to this “organoid” model, then the situation is going to be different. While there will still be some spontaneous activity, in the absence of any system for feeding in coordinated inputs to regions of sensory cortex, it’s unclear how activity-dependent development of these circuits will proceed. I would expect a messy, largely “random” pattern of connections, rather than the “fine-tuned” system that should result in normal development. In fact, the entire cortex is likely to develop with this kind of “nonsense” organization.

Should this disordered lump of tissue even be considered a brain, much less a person?

http://bossy-girls.net/ Lila Sovietskaya

If this brain in a jar exhibits thought waves, then it has a consciousness. Therefore this is ethically uncomfortable. My bunch of neurons and their synapses expressed this thought because eyes and hands were available

http://asdofindia.blogspot.com/ Akshay S Dinesh (ASD of India)

Remember a time when you were a baby?
There’s no thought without experience.
There’s no consciousness. This is the side effect of thinking consciousness is a special entity put into embryos by god.

Richard

I would agree with Zachary here. If you put your brain in a vat and kept it alive, the activity in the brain would purely be its own internally generated activity. Plasticity will rewire such a brain as all the sensory inputs would be receiving no input. I can’t guess what the brain’s conscious experience would be, but I guess there would be some crazy hallucinations, and then who knows how that would develop over time as the brain rewired itself according to its own internally-generated activity.

I don’t think brains grown in vats would have any kind of meaningful consciousness as we know it; I think input from an environment is an essential component of consciousness.

@LilaSovietskaya:disqus – “thought waves” are correlates of certain mental states; they do not imply consciousness (you can create oscillations in brain slices, for example).

http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

Richard: That’s all very possibly true, but I maintain that the question is open. It remains possible that in some sense the form of human consciousness is innate to the human brain, and what we get from the senses is the content.

Richard

I agree the question is open, but would argue that the form and content of consciousness are inseparable. Consciousness is a property of an agent in an environment rather than of a brain. Without an environment, what meaning does consciousness have?

http://brightumbra.wordpress.com/ BrightUmbra

“I can’t guess what the brain’s conscious experience would be, but I guess there would be some crazy hallucinations, and then who knows how that would develop over time” — if I were dying of a terminal illness, I would volunteer for such an experiment, just for such an experience.

I think the circadian rhythm would likely disintegrate due to the lack of external day/night stimulus, so the sleep cycle would gradually decay into an oscillating spectrum of lucidity. I imagine this would be like slipping into and out of dreams of an increasingly incoherent nature, with the line between awake and asleep becoming blurred past the point of obscurity.

Beyond this point, though, my capacity for speculation is exhausted.

http://brightumbra.wordpress.com/ BrightUmbra

If said vat included all the necessary equipment to accurately simulate sensory input, then the person “in” the brain would develop the same as any other human living in a similar environment.

Before you make you final decision, rewatch Dalton Trumbo’s Johnny Got His Gun.

Marc Lustig

” So if it were possible to somehow grow a complete human brain –
complete with the kind of connections found in normal human brains – I
think that brain would be a human being. […] We’re several lightyears away from that point right now.”

Following that argument, will a complete human brain, not grown in a dish, but using silicon chips, be human as well? Because we might find out a lot sooner than we probably think. (https://www.humanbrainproject.eu)

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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.